Human peripheral blood monocytes were isolated by counterflow centrifugal elutriation in a relatively unactivated state as accessed by the absence of collagenase production in control monocyte cultures. The addition of either concanavalin A (Con A) or lipopolysaccharide to the monocyte cultures resulted in the production of substantial levels of collagenase by these cells. Con A caused a more consistent activation with higher levels of collagenase. The amount of collagenase produced by the monocytes was 2 to 4 times that secreted by guinea pig peritoneal macrophages. Indomethacin inhibited Con A stimulated monocyte collagenase by at least 50% and this inhibition was reversed by 10 to the -8M PGE2. Examination of the production and regulatory influence on cell function of the known arachidonic acid (AA) metabolites has been made possible by the development of a high pressure liquid chemotography procedure which separates the individual prostaglandins, leukotrienes and monohydroxyeicosatetraenois acids (mono-HETE). Production of AA metabolites is being studied in lymphocytes, monocytes, basophils, platelets and polymorphonuclear leukocytes. The first results, obtained with the rat basophilic leukemia subline (RBL-1H3), have revealed that when these cells are stimulated with ionophore the ratio in AA metabolites released differs from that of IgE treated cells. Ionophore stimulated basophils release more total labeled material than antigen treated cells with the order of metabolites being 5 HETE greater than LTB4 greater than PGD2 greater than PGE2 whereas with antigen the ratio is PGD2 greater than PGE2 greater than 5 HETE and LTB4 greater than HETE and LTE4. The study on the influence of the immune system on bone resorption has revealed that the spleen cells of osteopetrotic rats produce lower levels of IL-2 than those of normal littermates. This may, in part, account for the lower lymphocyte proliferative levels observed with lymphocytes of affected rats when compared to normal littermates.